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Introduction: Lifestyle activities, such as regular physical activity, are important for good metabolic health and the prevention of non-communicable diseases. Epidemiological studies highlight an increase in the proportion of overweight children in Singapore. A workgroup was formed to develop recommendations to encourage children and adolescents (aged 7–18 years) to adopt a holistic approach towards integrating beneficial activities within a daily 24-hour period for good metabolic and general health. Methods: The Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision framework was employed to formulate the public health question, assess the evidence and draw conclusions for the guide. The evidence for international 24-hour movement guidelines, and guidelines for physical activity, sedentary behaviour, and sleep and eating habits were reviewed. An update of the literature review from August 2018 to end of September 2020 was conducted through an electronic search of Medline and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Results: Ten consensus statements were developed. The statements focused on the overall aim of achieving good metabolic health through integration of these activities and initiatives: light and moderate- to vigorous-intensity physical activity on a regular basis; muscle- and bone-strengthening activities; limiting sedentary behaviour; regular and adequate sleep; good eating habits and choosing nutritionally balanced foods and drinks; practise safety in exercise; and aiming to achieve more or all aforementioned recommendations for the best results. Conclusion: This set of recommendations provides guidance to encourage Singapore children and adolescents to adopt health-beneficial activities within a 24-hour period. Keywords: Eating habits, metabolic health, physical activity, sedentary behaviour, sleep

Purpose Exercise can help cancer survivors manage sequela, treatment side effects, improve overall quality of life, and is recommended for most. The purpose of this study was to investigate exercise behavior and factors influencing exercise engagement among cancer survivors at the National Cancer Centre, Singapore (NCCS). Methods This cross-sectional study was inclusive of survivors of all cancer types and stages who were at least 21 years of age and had undergone chemotherapy at the NCCS. Surveys were utilized to assess survivor barriers and facilitators to exercise and to retrospectively assess physical activity and exercise behaviors at 4 cancer-related time periods (pre-diagnosis and post-diagnosis before, during, or after chemotherapy). Results A total of 102 cancer survivors were enrolled; 60% were diagnosed with stage IV cancer. Predominant cancer types included lower gastrointestinal tract (25.5%) and breast cancer (21.6%). Prior to cancer diagnosis, 90.2% of participants reported aerobic activity satisfying NCCN guidelines. Significant reductions in reported exercise, and physical activity, were observed following cancer diagnosis that persisted during chemotherapy. Key exercise facilitators included the desire to remain healthy (86.3%) and to improve sleep and mental well-being (73.5%). Key barriers included side effects of treatment (52.0%). Only 46.1% of survivors reported receiving exercise guidance from healthcare professionals following diagnosis. Conclusion Overall, even among this notably active cohort of Singaporean survivors, opportunities for increased exercise engagement throughout the survivorship continuum remain. Increased education regarding the benefits of exercise to survivors as well as guidance regarding exercise modalities including resistance training is greatly needed as well.

Background Many countries have restricted public life in order to contain the spread of the novel coronavirus (SARS-CoV2). As a side effect of related measures, physical activity (PA) levels may have decreased. Objective We aimed (1) to quantify changes in PA and (2) to identify variables potentially predicting PA reductions. Methods A systematic review with random-effects multilevel meta-analysis was performed, pooling the standardized mean differences in PA measures before and during public life restrictions. Results A total of 173 trials with moderate methodological quality (modified Downs and Black checklist) were identified. Compared to pre-pandemic, total PA (SMD − 0.65, 95% CI − 1.10 to − 0.21) and walking (SMD − 0.52, 95% CI − 0.29 to − 0.76) decreased while sedentary behavior increased (SMD 0.91, 95% CI: 0.17 to 1.65). Reductions in PA affected all intensities (light: SMD − 0.35, 95% CI − 0.09 to − 0.61, p = .013; moderate: SMD − 0.33, 95% CI − 0.02 to − 0.6; vigorous: SMD − 0.33, − 0.08 to − 0.58, 95% CI − 0.08 to − 0.58) to a similar degree. Moderator analyses revealed no influence of variables such as sex, age, body mass index, or health status. However, the only continent without a PA reduction was Australia and cross-sectional trials yielded higher effect sizes (p Conclusion Public life restrictions associated with the COVID-19 pandemic resulted in moderate reductions in PA levels and large increases in sedentary behavior. Health professionals and policy makers should therefore join forces to develop strategies counteracting the adverse effects of inactivity.

We read with interest the study by Manuel et al showing that chronic immunosuppression could protect against severe COVID-19 in liver transplant patients.1 Despite increased comorbidities, COVID-19 in liver transplant patients was not more severe than in non-transplant cohorts.1 2 We present findings from a COVID-19/HIV coinfected decedent who exhibited a significantly longer survival time (46 days) than that of three COVID-19 decedents (average 30 days) (figure 1A). Given the immunosuppressive effects of HIV,3 the prolonged survival of our COVID-19/HIV patient may reflect protection from severe COVID-19. Figure 1 Increased myeloid and reduced T-cell abundance characterises the liver and kidney but not the lungs of a COVID-19/HIV decedent. (A) Kaplan-Meier survival curve of COVID-19/HIV case (nCOVID-19/HIV = 1) and COVID-19 cases (nCOVID-19=3). P-value: Log-rank (Mantel-Cox) test. (B) Representative regions of interest (ROI) of the liver, kidney, and lung from the COVID-19/HIV decedent and one COVID-19 decedent. (C) Principal component analyses of transcriptional profiles of COVID-19/HIV and COVID-19 decedents from ROIs of the lung (nCOVID-19/HIV = 11, nCOVID-19=29), liver (nCOVID-19/HIV = 10, nCOVID-19=32), and kidney (nCOVID-19/HIV = 11, nCOVID-19=8). (D) Relative estimated levels of immune cells determined by deconvolution of digital spatial profiling ROIs using CIBERSORTx (https://cibersort.stanford.edu/). Grey bars indicate the means. P-values were calculated by a two-tailed t -test: *(

The outbreak of COVID‐19 has precipitated international lockdown measures to curb disease transmissions. The closure of public activity spaces as well as changes in pandemic workload may disrupt healthcare workers' physical activity and self‐care routines. We sought to examine the association between physical activity levels and mental health burden of healthcare workers during the COVID‐19 lockdown in Singapore. This cross‐sectional study comprised of an multidomain survey that was administered digitally to 707 healthcare workers between 17 May and 18 June 2020. Exercise frequency, duration and intensity of these healthcare workers had reduced significantly during the lockdown compared to pre‐lockdown. 25.3%, 37.2%, and 11.9% had screened positive for moderate‐to‐extremely‐severe depression, anxiety and stress respectively. Reductions in exercise duration was a significant risk factor for mild stress and moderate‐to‐severe depression while increase in exercise frequency was found to be a protective factor against depressed mood. Our study revealed that a short‐term reduction in physical activity levels during lockdown was associated with poorer psychological outcomes. Given the protection that exercise confers on depression, physical activity should be promoted at the workplace and at home to support healthcare workers to cope through this protracted health crisis.

We read with great interest the article published by Zuo et al , which highlighted the presence of SARS-CoV-2 RNA in stool samples during active and convalescence phases of COVID-19 infection.1 However, no study has reported the presence of viral antigens within GI and hepatic organs during the convalescent phase. Using conventional immunohistochemistry, we detected SARS-CoV-2 nucleocapsid protein (NP) in the colon, appendix, ileum, haemorrhoid, liver, gallbladder and lymph nodes (figure 1A–K) from five patients who recovered from COVID-19, ranging from 9 to 180 days after testing negative for SARS-CoV-2 (online supplemental table 1). Notably, when multiple tissues were obtained from one patient (patients 1 and 4), all the tissues showed the presence of the viral antigen, suggesting widespread multiorgan involvement of the viral infection. Interestingly, for the colon, the viral antigen was only present in normal colonic crypts and polyps but not in the neoplastic tissues (figure 1Q). Similar negative staining in the hepatocellular carcinoma tumour region was also observed (figure 1R) albeit the positive staining in some of the scattered immune cells (figure 1D). Validating our findings, we detected SARS-CoV-2 spike protein (figure 1L–P) and RNA (figure 2B–F) in the above-mentioned tissues using conventional immunohistochemistry and RNAscope, respectively. However, we were unable to detect viral RNA in some patients’ tissues (online supplemental table 1), possibly because of higher RNA degradation rate as compared with protein and other patient-dependent factors such as disease severity, time since recovery and basal metabolic rate.### Supplementary data [gutjnl-2021-324280supp001.pdf] Figure 1 Immunohistochemical staining of the SARS-CoV-2 nucleocapsid and spike proteins in intestinal and hepatic tissues. (A and B) Positive SARS-CoV-2 nucleocapsid protein (NP) staining in colonic crypts (A) and appendix (B), both with a granular supranuclear cytoplasmic pattern. (C) positive SARS-CoV-2 NP staining in scattered immune cells …

Mutations in the PI3K pathway, particularly of PIK3CA, were reported to be intimately associated with triple negative breast cancer (TNBC) progression and development of treatment resistance. We profiled PIK3CA and other genes on 166 early-stage TNBC tumors from Singapore, for comparison to publicly available TNBC cohorts. These tumors were profiled transcriptionally using a Nanostring panel of immune genes and multiplex immunohistochemistry, then manually scored for PD-L1-positivity using two clinically relevant clones, SP142 and 22C3. We discovered a higher rate of PIK3CA mutations in our TNBC cohort as compared to non-Asian cohorts, along with TP53, BRCA1, PTPN11, and MAP3K1 alterations. PIK3CA mutations did not affect overall or recurrence-free survival, and when compared to PIK3CAWT tumors, there were no differences in immune infiltration. Using two clinically approved antibodies, PIK3CAmut tumors were associated with PD-L1 negativity. Analysis of co-mutation frequencies further revealed that PIK3CA mutations tended to be accompanied by MAP kinase pathway mutation. The mechanism and impact of PIK3CA alterations on the TNBC tumor immune microenvironment and PD-L1 positivity warrant further study.

Sports-related sudden cardiac death is a rare but devastating consequence of sports participation. Certain pathologies underlying sports-related sudden cardiac death could have been picked up pre-participation and the affected athletes advised on appropriate preventive measures and/or suitability for training or competition. However, mass screening efforts – especially in healthy young populations – are fraught with challenges, most notably the need to balance scarce medical resources and sustainability of such screening programmes, in healthcare systems that are already stretched. Given the rising trend of young sports participants across the Asia-Pacific region, the working group of the Asian Pacific Society of Cardiology (APSC) developed a sports classification system that incorporates dynamic and static components of various sports, with deliberate integration of sports events unique to the Asia-Pacific region. The APSC expert panel reviewed and appraised using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed, which were then put to an online vote. Consensus was reached when 80% of votes for a recommendation were agree or neutral. The resulting statements described here provide guidance on the need for cardiovascular pre-participation screening for young competitive athletes based on the intensity of sports they engage in.

Cancer is the leading cause of death worldwide. Unfortunately, efforts to understand this disease are confounded by the complex, heterogenous tumor microenvironment (TME). Better understanding of the TME could lead to novel diagnostic, prognostic, and therapeutic discoveries. One way to achieve this involves in vitro tumor models that recapitulate the in vivo TME composition and spatial arrangement. Here, we review the potential of harnessing in vitro tumor models and artificial intelligence to delineate the TME. This includes (i) identification of novel features, (ii) investigation of higher-order relationships, and (iii) analysis and interpretation of multiomics data in a (iv) holistic, objective, reproducible, and efficient manner, which surpasses previous methods of TME analysis. We also discuss limitations of this approach, namely inadequate datasets, indeterminate biological correlations, ethical concerns, and logistical constraints; finally, we speculate on future avenues of research that could overcome these limitations, ultimately translating to improved clinical outcomes.

BackgroundExamining Hematoxylin & Eosin (H&E) images using brightfield microscopes is the gold standard of pathological diagnosis as it is an inexpensive method and provides basic information of tumors and other nuclei. Complementary to H&E-stained images, Immunohistochemical (IHC) images are crucial in identifying tumor subtypes and efficacy of treatment response. Other newer technologies such as Multiplex Immunofluorescence (mIF) in particular, identifies cells such as tumor infiltrating lymphocytes (TILs) which can be augmented via immunotherapy, an evolving form of cancer treatment. Immunotherapy helps in the manipulation of the host immune response and overcome limitations like the PD-1 (Programmed Cell Death-1) receptor induced restrictions on TIL production. If the same biopsy specimen is used for inspection, the higher order features in H&E images can be used to obtain information usually found in mIF images using Convolutional Neural Networks (CNNs), widely used in object detection and image segmentation tasks.MethodsAs shown in (figure 1), firstly, a novel optical flow-based image registration paradigm is prepared to co-register H&E and mIF image pairs, aided by adaptive color thresholding and automated color clustering. Secondly, generative adversarial networks (GANs) are adapted to predict TIL (CD3, CD45) regions. For this purpose, a unique dataset is ideated and used in which a given single channel mIF image, e.g., a CD3 channel mIF image is superimposed on the corresponding H&E image. Primarily, the Pix2Pix GAN model is used to predict CD3 and/or CD45 regions.ResultsThe intensity-based image registration workflow is fast and fully compatible with the given dataset, with an increase in evaluation metric scores after alignment (table 1). Furthermore, this study would be the first implementation of optical flow as the registration algorithm for pathological images. Next, the use of the special dataset not only reduces penalization during the training of the Pix2Pix model, but also helped in gaining repeatable results with high scores in metrics like structural similarity index measure and peak-signal to noise ratio, with minimal effects on location accuracy (table 2 and table 3).ConclusionsThis multi-modal pathological image transformation study could potentially reduce dependence on mIF and IHC images for TILs scoring, reducing the amount of tissue and cost needed for examination, as its information is derived directly from inexpensive H&E images automatically – ultimately develop into a pathologist-assisted tool for TILs scoring. This would be highly beneficial in facilities where resources are relatively limited.Ethics ApprovalThe Agency of Science, Technology and Research, Singapore, provided approval for the use of control tissue materials in this study IRB: 2020 112Abstract 818 Figure 1Proposed workflowAbstract 818 Table 1Image registration metricsAbstract 818 Table 2CD3 negative regions examplesAbstract 818 Table 3CD3 positive regions examples

Summary The peroxidase APEX2 has been used widely for proximity biotinylation and subsequent proteomics analyses. However, the poor membrane permeability of the biotin phenol substrate and the inhibitory effect of peroxide on the enzyme’s activity has hampered proximity labeling in certain cell culture systems and tissues. Here, we describe an APEX2 protocol that uses alternative peroxide and biotin phenol concentrations. The protocol permits robust proximity biotinylation in confluent epithelial cell cultures and may be applicable to other cell cultures and tissues. For complete details on the use and execution of this protocol, please refer to Tan et al. (2020)., Graphical Abstract, Highlights • APEX2 permits proximity biotinylation in confluent cell cultures • Biotin phenol and peroxide concentrations are critical • Spatial controls are required to generate specific proximity proteomes, The peroxidase APEX2 has been widely used for proximity biotinylation and subsequent proteomics analyses. However, the poor membrane permeability of the biotin phenol substrate and the inhibitory effect of peroxide on the enzyme’s activity has hampered proximity labeling in certain cell culture systems and tissues. Here, we describe an APEX2 protocol that uses alternative peroxide and biotin phenol concentrations. The protocol permits robust proximity biotinylation in confluent epithelial cell cultures and may be applicable to other cell cultures and tissues.

Confinement measures during the COVID-19 pandemic have caused substantial reductions in global physical activity (PA) levels. In view of the manifold health benefits of PA, the development of interventions counteracting this trend is paramount. Our survey with 15,261 participants (38 ± 15 years, 58.5% females) examined preferences towards digital home exercise programs in 14 countries affected by COVID-19. More than two-thirds of the sample (68.4%, n = 10,433) indicated being interested in home exercise, and most participants were willing to work out at least three times per week (89.3%, n = 9328). Binary logistic regression revealed that female sex, working part-time, younger age, and being registered in a gym were associated with willingness to exercise. Flexibility (71.1%, n = 7377), resistance (68.6%, n = 7116), and endurance training (62.4%, n = 6478) were the most preferred types of exercise. Our results may guide health providers in developing individually tailored PA interventions during the current and future pandemics.

As intraocular surgery progressed, the tools in use have shrunk in size, from 20- to 25-gauge and beyond. The reduction in light intensity caused by this has pushed light pipe advancement in the direction of brighter and brighter light sources. Despite these advances, the rigid nature of regular light pipes still limits the range of illumination, especially when dealing with ciliary bodies. This can be overcome by using a concentric tube robot to build a steerable light pipe. Such a device is useful in solving issues of orientation and alignment faced by the surgical platforms being developed or adapted for intraocular surgery, by supplying end-effector intraocular dexterity. We propose a novel flexible robot design with a concentric-tube motion generation mechanism to make them more viable for intraocular procedures. The principles behind the actuation design were identified and modified with priority placed on compactness and workspace constraints for intraocular surgery. A three-degrees-of-freedom handheld light pipe steering guide prototype with a suitable tube configuration has been proven to supply more excellent maneuverability compared to an ordinary light pipe. After the optimization of tube parameters and a kinematic model, the application as a light pipe was further evaluated.

Background: Many governments have restricted public life during the COVID-19 pandemic. Related measures, among others, include closures of sports facilities and gyms. As regular movement is essential for immune function, bodily health and mental wellbeing, this study examined the effect of pandemic-related confinements on global physical activity (PA) levels. Methods: A multinational survey was performed in 14 countries. To quantify self-reported PA, the times spent in moderate and vigorous physical activities (MVPA) as well as in vigorous physical activities only (VPA) were assessed by means of the Nordic Physical Activity Questionnaire (short-form). Data were obtained for leisure and occupational PA pre and during restrictions of public life. Compliance with PA guidelines was calculated based on the recommendations of the World Health Organization (WHO). To estimate the risk of non-response bias, wave analyses were performed. Findings: A population of n=13,503 respondents (39±15 years, 59% females) were surveyed without indication of non-response bias. Compared to pre-restrictions, overall self-reported PA decreased by 41% (MVPA) and 42·2 % (VPA) during restrictions. Reductions were higher for occupational vs. leisure time, young and old vs. middle-aged persons, previously more active vs. less active individuals, but similar between men and women. Compared to pre-pandemic, compliance with WHO guidelines decreased from 81·0% to 62·5%. Interpretation: Results suggest PA levels have substantially decreased globally during the COVID-19 pandemic. Key stakeholders should consider strategies to mitigate loss in PA in order to preserve health during the pandemic and in future crises. Funding Statement: There was no external funding. Declaration of Interests: The authors declare there is no conflict of interest. Ethics Approval Statement: Ethics approval was obtained in each involved country (Australia, Austria, Argentina, Brazil, Chile, France, Germany, Italy, Netherlands, South Africa, Singapore, Switzerland, Spain, USA). All participants provided digital informed consent.

Epithelial apico-basal polarity is established through the asymmetric cortical distribution of the Par, Crumbs and Scribble polarity modules. Apical (Par and Crumbs) and basolateral (Scribble) polarity modules overlap at the apical-lateral border, which, in mammals, is defined by the apical junctional complex (AJC). The AJC is composed of tight junctions (TJ) and adherens junctions (AJ) and plays fundamental roles in epithelial morphogenesis and plasticity. However, the molecular composition and precise sub-junctional organization of the AJC and its associated polarity regulators are still not well defined. Here we used the peroxidase APEX2 for quantitative proximity proteomics (QPP) and electron microscopy (EM) imaging to generate a nanometer-scale spatio-molecular map of the apical-lateral border in fully polarized MDCK-II cells. Using Par3 and Pals1 as surrogates for QPP we present a spatially resolved network of ∼800 junction-associated proteins. The network dissects TJ and AJ components and provides strong evidence that TJ are composed of distinct apical and basal subdomains. Moreover, we find that Pals1 and its binding partners PatJ, Lin7c and Crumbs3 define a hitherto unidentified membrane compartment apical of TJ, which we coin the vertebrate marginal zone (VMZ). The VMZ is physically associated with HOMER scaffolding proteins, regulators of apical exocytosis, and membrane-proximal HIPPO pathway proteins. Taken together our work defines the spatial and molecular organization of the apical-lateral border in fully polarized mammalian epithelial cells, reveals an intriguing molecular and spatial conservation of invertebrate and vertebrate cell polarity protein domains, and provides a comprehensive resource of potentially novel regulators of cell polarity and the mammalian AJC.

Epithelial apico-basal polarity is established through the asymmetric cortical distribution of the Par, Crumbs and Scribble polarity modules. Apical (Par and Crumbs) and basolateral (Scribble) polarity modules overlap at the apical-lateral border, which, in mammals, is defined by the apical junctional complex (AJC). The AJC is composed of tight junctions (TJ) and adherens junctions (AJ) and plays fundamental roles in epithelial morphogenesis and plasticity. However, the molecular composition and precise sub-junctional organization of the AJC and its associated polarity regulators are not well defined. Here, we used the peroxidase APEX2 for quantitative proximity proteomics (QPP) and electron microscopy (EM) imaging to dissect the architecture of the AJC in fully polarized MDCK-II cells. We present a high-confidence proteome of the apical-lateral border in which TJ and AJ components and apical and lateral compartment markers are spatially resolved. We further demonstrate that the Crumbs complex (Pals1, PatJ, Lin7c, and Crumbs3) defines a hitherto unidentified membrane compartment apical of TJ, which we coin the vertebrate marginal zone (VMZ). QPP, imaging, and immunoprecipitation assays showed that the HOMER scaffolding proteins, PKN2 and PTPN13, and the membrane-proximal HIPPO pathway proteins ARHGAP29 and STXBP4 are recruited to the VMZ via the PDZ domains of PatJ. Taken together, our work defines the spatial and molecular organization of the apical-lateral border in mammalian epithelial cells, reveals an intriguing molecular and spatial conservation of invertebrate and vertebrate cell polarity protein domains, and identifies a VMZ-associated protein network implicated in HIPPO signaling and the control of the cortical actin cytoskeleton. Agency for Science, Technology and Research (A*STAR) Accepted version We thank Andre le Bivic, Spiros Efthimiopoulos, Ben Margolis, Jingshi Shen, Karl Matter, and Ceniz Zihni for providing antibodies, plasmids, and other reagents. This work was supported by an NTU Singapore start-up-grant to A.L. and by funding from the Agency for Science and Technology (A*STAR), Singapore, to W.H. and J.G. We thank Sara Sandin and Tom Carney for supporting this work through research grants RG39/14 and NIM/03/2016. B.T. was a recipient of a PhD scholarship from the A*STAR Graduate Academy. We further thank the NTU Institute of Structural Biology (NISB) for support.

Plantar fasciitis is a very common cause of inferior heel pain that can be triggered and aggravated by prolonged standing, walking, running and obesity, among other factors. Treatments are largely noninvasive and efficacious. Supportive treatments, including the plantar fascia-specific stretch, calf stretching, appropriate orthotics and night dorsiflexion splinting, can alleviate plantar fascia pain. While local injections of corticosteroids can help with pain relief, the effects are short-lived and must be weighed against the risk of fat pad atrophy and plantar fascia rupture. Ultrasonography-guided focal extracorporeal shock wave therapy is useful for patients with chronic plantar fasciitis and referrals for this treatment can be made in recalcitrant cases. Activity modification to decrease cyclical repetitive loading of the plantar fascia should be advised during the treatment phase regardless of the chosen treatment modality.

Background It is not known how passive muscle length and stiffness contribute to rigidity in Parkinson's disease. The objective of this study was to compare passive gastrocnemius muscle-tendon slack length and stiffness at known tension in Parkinson's disease subjects with ankle rigidity and in able-bodied people. Methods Passive ankle torque-angle curves were obtained from 15 Parkinson's disease subjects with rigidity and 15 control subjects. Torque-angle data were used to derive passive gastrocnemius length-tension data and calculate slack length and stiffness of the gastrocnemius muscle. Between-group comparisons were made with linear models. Results Gastrocnemius muscle-tendon slack lengths (adjusted between-group difference, 0.01 m; 95% CI, -0.02 to 0.04 m; P = 0.37) and stiffness (adjusted between-group difference, 15.7 m-1; 95% CI, -8.5 to 39.9 m-1; P = 0.19) were not significantly different between groups. Conclusions Parkinson's disease subjects with ankle rigidity did not have significantly shorter or stiffer gastrocnemius muscles compared with control subjects. © 2016 International Parkinson and Movement Disorder Society

Background Discharge summaries remain a critical communication tool with primary care physicians. In a previous study of over 200 general medicine discharge summaries, we demonstrated that only 50% contain information regarding the indication and follow up required of any medicine changes on discharge. Aim In this follow up pilot study, we assess the role of feedback and token incentives in improving discharge documentation. Methods Over a 14-week period, we randomly audited a selection of discharge summaries on a fortnightly basis. The results of these audits were fed back to the junior medical staff who compiled these summaries. If over 80% of the audited discharge summaries adequately documented the indication, with required follow up for new medication changes, junior doctors were provided with a token, non-monetary incentive for their efforts. At the end of the study period, we then conducted a survey of the junior doctors involved and collected feedback regarding their impressions of the study. Results Over the study period, 722 discharge summaries were completed and eligible for analysis. Over this time, mean appropriate documentation regarding medicine indication improved by 32%, and follow-up documentation improved by 10%. Overall, the participants felt the interventions were beneficial and that they should be continued beyond the study period. Conclusions Education coupled with regular feedback and non-monetary incentives can potentially lead to improvements in the quality of discharge summaries.

IntroductionHepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated mortality globally. Immune-checkpoint blockade (ICB) is one of the systemic therapy options for HCC. However, response rates remain low, necessitating robust predictive biomarkers. In the present study, we examined the expression of CD38, a molecule involved in the immunosuppressive adenosinergic pathway, on immune cells present in the tumor microenvironment. We then investigated the association between CD38 and ICB treatment outcomes in advanced HCC.MethodsClinically annotated samples from 49 patients with advanced HCC treated with ICB were analyzed for CD38 expression using immunohistochemistry (IHC), multiplex immunohistochemistry/immunofluorescence (mIHC/IF) and multiplex cytokine analysis.ResultsIHC and mIHC/IF analyses revealed that higher intratumoral CD38+cell proportion was strongly associated with improved response to ICB. The overall response rates to ICB was significantly higher among patients with high proportion of total CD38+cells compared with patients with low proportion (43.5% vs 3.9%, p=0.019). Higher responses seen among patients with a high intratumoral CD38+cell proportion translated to a longer median progression-free survival (mPFS, 8.21 months vs 1.64 months, p=0.0065) and median overall survival (mOS, 19.06 months vs 9.59 months, p=0.0295). Patients with high CD38+CD68+macrophage density had a better mOS of 34.43 months compared with 9.66 months in patients with low CD38+CD68+macrophage density. CD38himacrophages produce more interferon γ (IFN-γ) and related cytokines, which may explain its predictive value when treated with ICB.ConclusionsA high proportion of CD38+cells, determined by IHC, predicts response to ICB and is associated with superior mPFS and OS in advanced HCC.

To date there has been limited literature pertaining to Athlete’s Heart Syndrome in Asian athletes, especially for those in South East Asia. We performed a single center cross-sectional case-control study of elite athletes and controls, using current speckle-tracking echocardiography (STE) and tissue Doppler imaging (TDI)-based techniques. We reanalyzed previous data to further characterize the biomechanical changes in exercise induced cardiac remodeling elite athletes and controls at a tertiary hospital in Singapore. The Left Ventricular (LV) strain of the athletes’ group was significantly lower as compared to the control group (-19.0±2.0 vs -20.3±1.8, p=0.011). Furthermore, both LV torsion (14.3±17.8°/s vs 14.4±6.7°/s, p=0.031) and Lateral S’ (7.21±1.4 vs 8.7±1.6, p=0.001) showed small but statistically significant decreases in the athletes’ group versus the controls. The athletes group demonstrated a significantly lower Basal Right Ventricular (RV) free wall strain as compared to the controls (-19.8±5.5 vs -26.5±6.4 P < 0.001). The mid RV strain was marginally higher in the athletes’ group versus the controls (-25.0±4.3 vs -24.7±15.3 P=0.023). Our findings of impaired LV strain and torsion as well basal RV free walls strain in the South East Asian athletes group mirror studies done in Western cohorts. The higher mid RV free wall strain could represent compensatory response to the impaired basal RV function in athletes.

Oral anticoagulant (OAT)-associated intracranial hemorrhage (ICH) is a life-threatening emergency for which prothrombin complex concentrates (PCC) are considered first-line reversal agents. The only approved PCC in the USA for warfarin-associated ICH is non-activated PCC. Little data are available regarding the safety and effectiveness of factor VIII inhibitor bypassing activity (FEIBA) which is an activated prothrombin complex concentrate (aPCC). The aim of this analysis was to assess the safety and effectiveness of FEIBA compared to fresh frozen plasma (FFP) for reversal of OAT-associated ICH. Data were retrospectively collected to compare coagulation markers and in-hospital clinical outcomes in patients who received aPCC with or without FFP versus FFP alone for the reversal of OAT-associated ICH. Eighty-four patients met inclusion criteria; 50 patients received FFP alone, and 34 patients received FEIBA (mean dose 20 U/kg) with or without FFP for OAT-associated ICH. The proportion of diagnosed thrombotic events during hospitalization was similar in both groups (8% in the FFP group vs. 12% in the FEIBA group; P = 0.56). Median time to INR

To describe current patterns in initiation and cessation of proton pump inhibitors (PPIs) for stress ulcer prophylaxis (SUP) in intensive care units, and to assess the costs associated with inappropriate (non-evidence-based) SUP.Retrospective observational study in five ICUs in Western Australia. We assessed the medical records of consecutive patients admitted to the ICUs between September 2013 and January 2015. Patients aged18 years were excluded.We included 531 patients in the study. Of the 184 patients in whom PPIs were initiated for SUP in the ICU, 90 (48.9%) were still taking the therapy at the time of discharge from hospital. A documented indication for ongoing therapy was present in only nine patients (10%). We assumed a 10-year life expectancy after ICU discharge and that most patients continued taking a PPI, and calculated an additional cost of $180.20 per patient admitted to the ICU. This was based only on unnecessary PPI costs (ignoring costs of managing additional adverse events). The direct cumulative annual cost to the WA health system of PPIs continued unnecessarily for patients at discharge from hospital is estimated to be $250 800 for each year they continue to receive them.A substantial proportion of patients prescribed SUP in the ICU continue receiving this therapy at hospital discharge despite no clear indication. In addition to potential adverse clinical effects, this is associated with major direct and indirect cost implications.

Objectives To evaluate the efficacy of autologous conditioned plasma (ACP) compared with extracorporeal shockwave (ESWT) and conventional treatments for plantar fasciitis. Design Randomized trial. Setting Sports medicine center in a tertiary care hospital. Patients Fifty-four subjects (age range, 29-71 years) with unilateral chronic plantar fasciitis with more than 4 months of symptoms. Methods Subjects randomized to 3 groups: 19 to ACP and conventional treatment (ACP group), 19 to ESWT and conventional treatment (ESWT group), and 16 to conventional treatment alone. Conventional treatment included stretching exercises and orthotics if indicated. Main Outcome Measurements Outcomes were pain-Visual Analog Scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, and ultrasound plantar fascia thickness assessed at baseline before treatment and at 1 month, 3 months, and 6 months after treatment. Results VAS, AOFAS ankle-hindfoot scale, and plantar fascia thickness improved in all groups. Significant VAS pain score improvements in the ACP group compared with conventional treatment at month 1 ( P = .037) and for the ESWT group compared with conventional treatment at months 1, 3, and 6 ( P = .017 , P = .022, and P = .042). The AOFAS ankle-hindfoot scale score improved in the ACP group at months 3 and 6 ( P = .004 and P = .013) and, for the ESWT group, at months 1 and 3 ( P = .011 and P = .003) compared with conventional treatment. Significant improvements in plantar fascia thickness were seen in the ACP group at months 1 and 3 compared with conventional treatments ( P = .015 and P = .014) and at months 3 and 6 compared with the ESWT group ( P = .019 and P = .027). No adverse events reported. Conclusions Treatment of plantar fasciitis with ACP or ESWT plus conventional treatments resulted in improved pain and functional outcomes compared with conventional treatment alone. There was no significant difference between ACP and ESWT in terms of VAS and AOFAS ankle-hindfoot scale improvements, although the ACP group demonstrated greater reductions in plantar fascia thickness.

Background/aim The Sailing World Championships 2014 was contested by 1167 sailors in all 10 Olympic classes. Our objective was to characterise sailing-related injuries and illnesses in sailors participating in this regatta. Methods We conducted 2 surveys: (1) prior to the World Championships, sailors answered a 12-month recall questionnaire on sailing-related injuries and illnesses and (2) during the Championships, injuries and illnesses were documented. Results There were 760 respondents (65% of all participants) for the 12-month recall questionnaire (58% male, 42% female), of whom 244 participants reported 299 injuries (0.59 injuries per 1000 h of sailing). Injuries were most prevalent in the 49erFX (64%), RS:X Women (39%), 49er (37%) and Nacra 17 (36%). Lower back (29% of sailors), knee (13%), shoulder (12%) and ankle (10%) injuries were most prevalent; most (58% of all injuries) were overuse injuries; and 56% of sailors lost sailing time. Most illnesses (40%) were infections, primarily of the respiratory system (43%). During the Championships, there were 67 injuries (4 per 1000 days of sailing). The 49er (24% of all injuries), 470 Men and Women (24%), and 49erFX (19%) had the highest incidence. Injuries to the hand/fingers (22% of all injuries), back (18%), and foot (12%) were most common, as were contusions (37% of all injuries), cuts/lacerations (24%), and sprains (9%). Of the 29 illnesses (2 per 1000 days of sailing), 9 (31%) were gastrointestinal and 6 (21%) respiratory, while 2 (7%) were gout attacks. Conclusions The Olympic classes introduced since 2000 (49erFX, 49er, Nacra 17) have resulted in a rise in injuries.

Introduction: The aim of this study is to investigate the amount of water loss and percentage dehydration experienced during 1 hour of paddling on the kayak ergometer so as to help coaches and athletes tailor a suitable and adequate rehydration regime. Also, rehydration efficacy between water and a well established, commercially available sports drink (Gatorade, Quaker Oats company, USA) was investigated in this cross-over study. Materials and Methods: Ten national flatwater kayakers were monitored in a controlled setting while paddling the kayak ergometer for 1 hour at an intensity sustainable for long distance marathon. They rehydrated themselves ad libitum with provided beverage. Post-void towel-dried body mass was measured before and after the exercise with percentage dehydration calculated. Body core temperature (tympanic temperatures), ratings of perceived exertion and thirst index were monitored every 15 minutes. The amount of fluid consumed, urine output and urine specific gravity were obtained after exercise. Results: The results [mean ± standard deviation (SD)] showed that kayakers underwent 1.10 ± 0.52% dehydration while rehydrating with water as compared to 0.72 ± 0.38% while rehydrating with Gatorade. Also, athletes on water rehydration had higher rating of perceived exertion (RPE) at the 30th and 60th minute mark of the exercise. Overall, athletes undergoing water rehydration lost significantly more body mass (0.70 ± 0.39 kg) as compared to rehydrating with Gatorade (0.46 ± 0.27). Conclusion: Although the hydration efficacy of Gatorade proved superior to that of water, the athletes’ hydration habits with either fluids did not provide adequate hydration. It is recommended that specific strategies be developed to address dehydration and rehydration issues of kayakers in Singapore. Key words: Canoe, Gatorade, Fluid replacement, Marathon

Dinghy sailing is a physically challenging sport with competitors on water for several hours. Regulations and space in the boat limit the amount of food and fluid competitors can carry. Consequently, it is possible that the hydration and nutritional status of dinghy sailors may be compromised while racing. Despite this, the food and fluid intake of sailors while racing are unknown. The aim of this study was to assess the dietary intake of a group of club sailors while racing and compare this with current sports nutrition guidelines. Thirty-five sailors (9 females, 26 males) were monitored during a club regatta. Body mass changes were measured before and after racing, as were food and fluid intake. Results showed that most participants were in negative fluid balance after racing (males: mean -2.1%[95% confidence limits -1.7 to -2.5%]; females: -0.9%[0 to -1.8%]), most likely due to low voluntary fluid intake (males: 1215 ml [734 to 1695 ml]; females: 792 ml [468 to 1117 m]). Carbohydrate intake (males: 59 g [21 to 97 g]; females: 30 g [0 to 61 g]) was below recommendations for normal sports activity. Results revealed that the nutritional practices of club sailors do not comply with current sports nutrition guidelines. However, the performance implications of a compromise in nutrient intake remain to be investigated. Practical advice on methods of overcoming space limitations for the carriage of adequate fluid and food is offered.

Background Noninvasive intracranial pressure (ICP) measurement would represent a major advance for patients with neurological problems. The Vittamed ICP meter is an ultrasound-based device reported to have high agreement with lumbar puncture cerebrospinal fluid (CSF) pressure measurement. However, previous studies included mostly patients with normal levels of ICP. The purpose of our study was to perform an independent clinical validation study of a transcranial Doppler-based noninvasive ICP meter in patients anticipated to have a wide range of ICP. Methods In a prospective cross-sectional design, we simultaneously measured ICP with the Vittamed device and the invasive lumbar CSF pressure. The operator of each procedure was blinded to the result of the other method. Data were analyzed using Bland-Altman plots, Pearson correlation coefficients, and receiver operator characteristic curves. Results Twenty-four independent paired measurements of Vittamed and lumbar CSF pressure were obtained; with mean absolute difference between paired measures of 4.5 mmHg (standard deviation 3.1). The 95% limits of agreement were −10.5 to +11.0. The systematic bias (mean of paired differences) was negligible at 0.25 mmHg. The sensitivity, specificity, and area under the curve for ICP >20 mmHg were 0.73, 0.77, and 0.71, respectively. Conclusions The Vittamed ICP meter had fair agreement with lumbar CSF pressure measurement. The wide limits of agreement would preclude using this version of the device as a stand-alone method for ICP determination, but may be useful if combined with other ICP screening methods. Ongoing improvements to the Vittamed hardware and software may lead to improvements in accuracy and clinical utility of this device.

It is not known how passive muscle length and stiffness contribute to rigidity in Parkinson's disease. The objective of this study was to compare passive gastrocnemius muscle-tendon slack length and stiffness at known tension in Parkinson's disease subjects with ankle rigidity and in able-bodied people.Passive ankle torque-angle curves were obtained from 15 Parkinson's disease subjects with rigidity and 15 control subjects. Torque-angle data were used to derive passive gastrocnemius length-tension data and calculate slack length and stiffness of the gastrocnemius muscle. Between-group comparisons were made with linear models.Gastrocnemius muscle-tendon slack lengths (adjusted between-group difference, 0.01 m; 95% CI, -0.02 to 0.04 m; P = 0.37) and stiffness (adjusted between-group difference, 15.7 mParkinson's disease subjects with ankle rigidity did not have significantly shorter or stiffer gastrocnemius muscles compared with control subjects. © 2016 International Parkinson and Movement Disorder Society.

Sports medicine is a relatively new subspecialty in Singapore. This commentary chronicles its evolution in Singapore from 1969, through various milestones, to the present day. The first sports medicine clinic in Singapore was established in 1971 at Farrer Park. Notable institutions that followed include the Sports Medicine and Research Centre (1973), Soldier Performance Centre, Changi Sports Medicine Centre (2003), Singapore Sports Medicine Centre (2006), and other multidisciplinary centres of restructured hospitals. Formal groundwork to establish sports medicine as a subspecialty began in 2005, with its first trainee commencing traineeship at the Changi Sports Medicine Centre in 2007, and culminated in the subspecialty register at the beginning of 2011. Also captured in this discussion are the broader scopes of sports medicine, including military sports medicine, the sports sciences, exercise medicine, and event medical coverage.

Background: “Rapidly Improving Stroke Symptoms” (RISS) is a controversial exclusion criterion for tPA treatment for acute ischemic stroke (AIS). Prior studies suggest 20-30% of those excluded from tPA solely because of RISS have poor outcomes. Objectives: (1) To estimate frequency and magnitude of RISS using prespecified RISS definitions; (2) To explore how different RISS definitions predict clinical outcome. Methods: A prospective, observational, pilot study of AIS patients presenting within 4.5 hours of symptoms. After informed consent, subjects were administered serial NIH Stroke Scales (NIHSS) by certified examiners every 20 (±5) minutes until a treatment decision (tPA vs no-tPA) was made by the treating physician, independently from the study. RISS was calculated as baseline NIHSS (bNIHSS) - treatment decision NIHSS (tdNIHSS). Definitions of RISS (based on prior literature and expert consensus) were: (1) change in NIHSS score ≥ 4 point improvement (IMP) or (2) % change in NIHSS score (a) ≥ 25% or (b) ≥ 50% IMP. Good outcome was defined as modified Rankin Scale (mRS)=0-1 at 3-month post stroke. Logistic regression was used to determine if definition(s) of RISS predicted good outcome. Results: Fifty AIS: mean age 65 yrs (±15 SD); male 56%; black 78%; prior stroke/TIA 28%; median bNIHSS score 8(IQR 2,11); before treatment decision was made, 2 serial NIHSS scores were obtained for the entire cohort, 3 scores in 26/50 (52%); median tdNIHSS score 5 (IQR 2,9); treated with tPA 23/50(46%). Frequency of RISS varied based on definition used: 10% for ≥ 4 point IMP, 22% for ≥ 25% IMP, and 12% for ≥ 50% IMP. In the overall cohort, 42% of patients had good outcomes: 17/27 (63%) not treated with tPA (bNIHSS 3; IQR 2,5) vs 6/23 (26%) treated with tPA (bNIHSS 9;IQR 5,15), p=0.02. There was a difference in tdNIHSS between those not given tPA (2;IQR 1,4) and those given tPA (8;IQR 6,13), p Conclusions: Our prospective, pilot data suggest that a serial NIHSS assessment prior to treatment decision is feasible and may help determine the frequency and magnitude of RISS for larger studies. In our cohort, AIS patients improved approximately 3 points on the NIHSS from baseline to tPA treatment decision.